Cambridge Healthtech Institute’s 6^th Annual

Optimizing Bioassays for Biologics  

Merging Science and Statistical Methods for Successful Biological Assay Development 

October 24-25, 2018

Bioassays, at their core, spring from a fusion of biological and statistical sciences, and are used to measure activity or function of a compound or group of compounds in samples. As the field evolves, new technologies and software are changing the way scientists view experimental design and data analysis. The health authorities and USP have provided guidance for the design and validation of a bioassay; however, they do not discuss solutions to common problems springing from this revolution in technology. At Cambridge Healthtech Institute's sixth annual Optimizing Bioassays for Biologics, leaders working in bioanalytical and bioassay development will come together to provide case studies and best practices for handling the most common issues in biological assay development, validation, transfer, and maintenance. There will also be a focus on lifecycle management and design of experiments methods. In addition, new technologies and bioassay formats will be presented along with recommendations for implementation to ensure a steady drug development pipeline.

Final Agenda

OCTOBER 23-24

Recommended Pre-Conference Training Seminar*

TS1: Introduction to Design of Experiments (DoE)

* Separate registration required.

Wednesday, October 24

1:00 pm Conference Registration (Foyer)

LIFECYCLE MANAGEMENT
Edison EFG

1:40 Chairperson’s Opening Remarks

Perceval Sondag, Senior Manager, Statistics, PharmaLex

1:45 KEYNOTE PRESENTATION: A Lifecycle Approach to Bioassay Validation

Timothy Schofield, Senior Advisor, Technical Research & Development, GSK

A bioassay can be viewed as a manufacturing process, with measurements the product. The customer is a decision-maker, and the “quality attributes” are related to accuracy and precision. The analytical target profile lists the requirements for uses throughout the bioassay lifecycle. This talk will outline the stages and elements of a lifecycle approach to bioassay validation, highlighting the opportunities for ensuring the quality of bioassay measurement.

2:15 A Quality Approach to Stage One Bioassay Optimization

Steven Novick, PhD, Director, Statistical Sciences, MedImmune

The goal of stage one lifecycle management is to develop a reliable process for commercial manufacturing. It is imperative to develop robust bioassays to measure critical and key quality attributes, such as potency and purity of the drug substance and drug product. This presentation will illustrate modern statistical methods applied to a response-surface design to determine the design space for multiple bioassays simultaneously by optimizing the probability to meet specifications.

2:45 Assay Performance Qualification: A Fit for Purpose Approach

Perceval Sondag, Senior Manager, Statistics, PharmaLex

Recently, the lifecycle management concept for analytical procedures was introduced. It is strongly related to the Quality by Design concept given in the ICH-Q8 guidance. This contrasts with ICH-Q2 recommendations that only focus on the validation step to evaluate the performance of an analytical procedure. ICH-Q2’s well-known check-list approach fails to provide assurance of the quality of future results with respect to the intended use of the procedure. This talk proposes a fit for purpose method for assay validation in a lifecycle paradigm, while maintaining a reasonable compromise between producer and patient risks.

3:15 BioAssay Express: Introducing BLAT, an Assay Registration System for Biologics

Samantha Jeshonek, PhD, Research Informatics Analyst, Research Informatics, Collaborative Drug Discovery

BioAssay Express annotates bioassay protocols using semantic web vocabulary, which makes them accessible to both humans and machines. New data is created using a web-based interface, and legacy text-based data is curated with the support of text mining and machine learning methods. We will describe BioLogics Assay Template (BLAT).

3:30 Refreshment Break in the Exhibit Hall with Poster Viewing (Edison D)

4:10 CPV Application in Bioassays – Strategies to Maintain Lot to Lot Consistency & Prevent Assay Drift

Mitra Azadeh, PhD, Principal Scientist, Bioanalytical & Biomarker Development, Nonclinical Development, R&D, Shire

Continued process verification (CPV) is critical to bioassay life cycle management and essential in ensuring that the product output is within pre-established specifications. CPV components include systems for deviation identification, data collection and analysis, and in-process evaluation of qualification standards, and assay quality controls remain central throughout the process. This talk focuses on the role of quality controls in assay trending and monitoring of calibration drift. Factors critical to the production, qualification, and maintenance of quality controls as well as statistical versus graphical methods for control trending will be presented.

4:40 PANEL DISCUSSION: Statistical Approaches to Lifecycle Validation

• Opportunities to optimize each step of the lifecycle approach using statistical methods
• Common pitfalls and challenges in utilizing statistics for bioassay development
• Understanding regulatory guidelines (USP/NIBSC/FDA/etc.)
• Strategies for successful collaboration between statisticians and bioassay scientists

Moderator: Perceval Sondag, Senior Manager, Statistics, PharmaLex

Panelists: Timothy Schofield, Senior Advisor, Technical Research & Development, GSK

Steven Novick, PhD, Director, Statistical Sciences, Medimmune

Mitra Azadeh, PhD, Principal Scientist, Bioanalytical & Biomarker Development, Nonclinical Development, R&D, Shire

5:40 Dinner Short Course Registration

Recommended Dinner Short Course*

SC5: Back to Basics: Optimizing Bioassay Design and Analysis

* Separate registration required.

Thomas Little, PhD, President and CEO, Bioassay Sciences, Thomas A. Little Consulting

David Lansky, PhD, President, Precision Bioassay, Inc.

Testing for similarity via equivalence tests is an essential part of modern bioassay analyses. Sensitivity analyses show that scaled shifts in parameters measure non-similarity in ways that are assay-independent. These scaled shifts have lower bias and variance than ratio estimates of parameter-specific non-similarity. Well-chosen equivalence bounds for scaled shifts yield assays with limited bias in potency due to non-similarity. This gives us a way to set equivalence bounds for non-similarity informed by the product specification and analytic target profile.

Martin Kane, MS, CRE, Managing Data Scientist, Statistical and Data Sciences Practice, Exponent

Analytics equivalence has historically been handled with a statistical test for differences. As the regulatory environment matures, newer statistical methods are being developed to help ensure that two analytic methods are in fact equivalent, and don’t just suffer from a lack of difference. This talk will explore the statistical technique outlined in the draft FDA guidance document and discuss some of the perceived pitfalls associated with it.

9:00 NEW: Visual Tools for the Development of Equivalence Test Systems

Dr. Ralf Stegmann, Stegmann Systems

The development of test systems (assay and system suitability) making use of the equivalence test approach according to the USP <1032> is a challenging task especially for non-linear systems (e.g. 4-parameter fit). The question which and how many different tests are required to qualify an assay run cannot be answered easily. New visualization and assay simulation tools help the scientist to verify that a developed test system is capable to sufficiently proving similarity between test and standard curves as well as similarity between the assay run and development/validation data which has been used to develop the test system.

9:30 Problem Solving Roundtable Discussions

Wright / BannekerTable 6: Use of New Technologies in Bioassay Development

Moderator: Robyn Beckwith, PhD, Technical Development Scientist, Analytical Development and Quality Control, Genentech

Moderator: Martin Kane, MS, CRE, Managing Data Scientist, Statistical and Data Sciences Practice, Exponent

Thomas Little, PhD, President and CEO, Bioassay Sciences, Thomas A. Little Consulting

The presentation covers the design and validation of a bioassay. It demonstrates how plate layout, dose selection, outlier identification and removal, curve weighting, replicate strategy, curve fitting method, systems suitability and validity criteria all impact the invalid and OOS rate of the assay. A design of experiments approach to method robustness is presented. Establishing a design space for a bioassay, designing the validation protocols and acceptance criteria justification are presented.

Keith M. Bower, Principal CMC Statistician, Process Sciences, Seattle Genetics

Limited guidance is provided in regulatory documents for bioassay validation acceptance criteria (AC). This presentation illustrates (i) the interrelationship between intermediate precision (IP) and the coefficient of determination, and (ii) how to assess the likelihood of meeting proposed AC for a given study design. The use of a statistical performance assessment, relating IP to other AC is illustrated.

Nancy Sajjadi, M.Sc., Independent Quality Consultant

Martin Kane, MS, CRE, Managing Data Scientist, Statistical and Data Sciences Practice, Exponent

Stephen Hartman, PhD, Principal Scientist, AbbVie

Bioassays are a critical component of the development and testing strategy of biologic therapies. They are amongst the most challenging test methods to develop, implement, and maintain. The inherent variability of living cells, combined with complicated multi-step procedures, biologically active reagents, long incubation times, diverse readouts and instruments, and complex data analysis come together to make bioassay development extremely challenging. Furthermore, modern biotherapeutics are ever adopting new formats, modalities, novel mechanisms of action, and sometimes multiple mechanisms of action. As these therapies become more structurally and functionally diverse and complex, so do the bioassays needed to enable their development and release. This presentation will provide an overview of strategies, considerations, and recommendations for developing bioassays that are accurate, precise, robust, MoA-reflective, “QC-friendly,” and phase-appropriate. We will also discuss common pitfalls and oversights and how to avoid/prevent them.

Robyn Beckwith, PhD, Technical Development Scientist, Analytical Development and Quality Control, Genentech

Bioanalytical testing environments routinely face constraints due to sample throughput, procedural variability, required hands-on time, cost and repetitive strain on analysts. Automation of discrete assay steps or entire end-to-end workflows can potentially alleviate these issues, but practical implementation can be challenging given the inherent complexity of biological assay systems. Strategies for successful development and application of automation for biological assays will be explored, including fit for purpose approaches to implementing new technologies.

Bharathi Govindarajan, Ph.D., Senior Scientist, CMC Bioanalytical development, Immunogen, Inc.